Coupling Procedure Research Articles

Multiphysics Modeling of Heat Pipe Microreactor with Critical Control Drum Position Search

A multiphysics coupling methodology for heat pipe microreactors is presented in this work that includes a focus on a critical control drum position search routine and burnup capabilities. As the Serpent code is used for neutronics calculations, the recently developed GRsecant method for finding critical control drum positions is employed, which has explicit measures to manage the uncertainty introduced from the Monte Carlo calculation method. This work complements existing multiphysics modeling tools for heat pipe microreactors because it can be used to generate cross sections with fuel compositions determined by depletion with critical control drum positions. These methods are applied to a microreactor design motivated by the eVinciTM heat pipe microreactor. The convergence of the multiphysics coupling routine is analyzed at multiple burnup points. The multiphysics iterations with critical control drum search were observed to converge for all calculations performed in this work. Overall, the multiphysics coupling procedure enables the calculation of both thermal and neutronics characteristics with control drums in their critical positions for the core lifetime.

Self-propulsion performance prediction in calm water based on RANS/TEBEM coupling method

This paper proposes a hybrid RANS/TEBEM method to conduct self-propulsion prediction in calm water with accuracy and improve its efficiency by means of larger time step. In the coupling procedure, the rotating propeller is represented by time-averaged, spatial inhomogeneous body force field obtained from the potential flow solver based on Taylor Expansion Boundary Element Method (TEBEM) in RANS simulation. Effective wake is evaluated by subtracting induced velocities computed by potential solver from total velocities in RANS solver at a coupling plane upstream of propeller plane. The influence of coupling plane position and grid density on the numerical results is also investigated. Through KCS and KVLCC2 cases, it is shown that the predicted value of propeller revolution speed is within 4% of the experimental value, verifying the robustness and reliability of this method.

Heteroatom‐induced tensile strain in copper lattice boosts CO2 electroreduction toward multi‐carbon products

AbstractStrain engineering on metal‐based catalysts has been utilized as an efficacious strategy to regulate the mechanism and pathways in various electrocatalytic reactions. However, controlling strain and establishing the strain‐activity relationship still remain significant challenges. Herein, three different and continuous tensile strains (CuPd‐1.90%, CuAu‐3.37%, and CuAg‐4.33%) are successfully induced by introducing heteroatoms with different atomic radius. The catalytic performances of CuPd‐1.90%, CuAu‐3.37%, and CuAg‐4.33% display a positive correlation against tensile strains in electrochemical CO2 reduction reaction (CO2RR). Specifically, CuAg‐4.33% exhibits superior catalytic performance with a 77.9% Faradaic efficiency of multi‐carbon products at −300 mA cm−2 current density, significantly higher than those of pristine Cu (Cu‐0%). Theoretical calculations and in situ spectroscopies verify that tensile strain can affect the d‐band center of Cu, thereby altering the binding energy of *CO intermediates and Gibbs free energies of the C–C coupling procedure. This work might highlight a new method for precisely regulating the lattice strain of metallic catalysts in different electrocatalytic reactions.

Aminolysis-mediated single-step surface functionalization of poly (butyl cyanoacrylate) microbubbles for ultrasound molecular imaging

Molecular ultrasound imaging with actively targeted microbubbles (MB) proved promising in preclinical studies but its clinical translation is limited. To achieve this, it is essential that the actively targeted MB can be produced with high batch-to-batch reproducibility with a controllable and defined number of binding ligands on the surface. In this regard, poly (n-butyl cyanoacrylate) (PBCA)-based polymeric MB have been used for US molecular imaging, however, ligand coupling was mostly done via hydrolysis and carbodiimide chemistry, which is a multi-step procedure with poor reproducibility and low MB yield. Herein, we developed a single-step coupling procedure resulting in high MB yields with minimal batch-to-batch variation. Actively targeted PBCA-MB were generated using an aminolysis protocol, wherein amine-containing cRGD was added to the MB using lithium methoxide as a catalyst. We confirmed the successful conjugation of cRGD on the MB surface, while preserving their structure and acoustic signal. Compared to the conventional hydrolysis protocol, aminolysis resulted in higher MB yields and better reproducibility of coupling efficiency. Optical imaging revealed that under flow conditions, cRGD- and rhodamine-labelled MB, generated by aminolysis, specifically bind to tumor necrosis factor-alpha (TNF-α) activated endothelial cells in vitro. Furthermore, US molecular imaging demonstrated a markedly higher binding of the cRGD-MB than of control MB in TNF-α activated mouse aortas and 4T1 tumors in mice. Thus, using the aminolysis based conjugation approach, important refinements on the production of cRGD-MB could be achieved that will facilitate the production of clinical-scale formulations with excellent binding and ultrasound imaging performance.Graphical

High-Performance Suspension Bead Sensor Based on Optical Tweezers and Immuno-Rolling Circle Amplification.

In recent years, optical tweezers have become an effective bioassay tool due to their unique advantages, especially in combination with suspension beads, which can be applied to develop a high-performance analysis platform capable of high-quality imaging and stable signal output. However, the optical tweezer-assisted bead analysis is still at the early stage, and further development of different favorable methods is in need. Herein, we have first developed the optical tweezer-assisted immuno-rolling circle amplification (immuno-RCA) on beads for protein detection. Prostate-specific antigen was selected as the model analyte, and the immunosandwich structure on beads was built by the high affinity of "antibody-antigen". The "protein-nucleic acid" signals were effectively converted through the covalent coupling procedure of antibodies and oligonucleotides, further initiating the RCA reaction to achieve signal amplification. The individual beads with the strong irregular Brownian motion in a fluid environment were eventually trapped by the optical tweezers to acquire the accurate and high-quality signal. Compared with the conventional immunoassay on beads, the sensitivity of the developed strategy was increased by 587 times with a limit of detection of 4.29 pg/mL (0.13 pM), as well as excellent specificity, stability, and reproducibility. This study developed the new optical tweezer-assisted beads imaging strategy for protein targets, which has great potential for being applied to clinical serology research and expands the application of optical tweezers in the bioassays.

An integrated model for flexible simulation of biomass combustion in a travelling grate-fired boiler

Grate-fired boiler is of considerable interest for burning biomass owing to its reduced sensitivity to variations in fuel composition and size. However, grate-fired technology exhibits unsatisfactory performance in terms of combustion efficiency, contaminant emissions, and flame stability. CFD modelling can provide reasonable optimizations to overcome these drawbacks and ultimately achieve clean and efficient energy production. Conventional approach simulates the fuel-bed and freeboard combustion separately using an in- and over-bed coupling procedure, where data of the gases leaving from the packed-bed top and the radiative heat flux emitted by the high-temperature flame onto the bed cannot be interacted in real-time. This may cause distinct deviations in the calculations. In this paper, a three-dimensional (3D) full-scale integrated model is developed for the simulation of grate-fired boiler, in which the intensive combustion of both the freeboard and fuel-bed is solved in one scheme using the Eulerian-Lagrangian method. The gas phase is considered as a continuous medium and calculated by the Eulerian model, while the solid particles are considered as a discrete phase and tracked via the Lagrangian method. The reliability of the model is well verified through various field measurements and observations. Results shows that the key parameters are non-uniformly distributed along the grate width, i.e., the aerodynamic and combustion environment is poor at the vicinity of water-cooled walls compared with that at the furnace center. This results in a significant lag in volatile gases release and char oxidation near the water-cooled wall on both sides, which finally causes obvious differences in the distribution of temperature and species. For instance, the peak of CO concentration at the center is 12.6 % at 3.3m from the feed entrance, while that near the water-cooled wall is 8.6 % around 3.5m. The char burnout ratio in the bottom ash can be accurately calculated by this model, with a negligible relative error between the simulation of 81.97 % and the measurement of 82.50 %. It also provides a novel method for the calculation of fly ash particles by using size-grouped and non-spherical particles. Small-size particles in the vicinity of the feed inlet, as well as a part of the particles burning at the end of the grate are entrained into the freeboard by the primary air supplied beneath the grate and the high-momentum secondary air on the bed top. This model can provide valuable theoretical guidance for optimizing the refined distribution of fuel and air in grate-fired power plants and mitigating irregular deposition (corrosion) on heat exchangers and water-cooled walls caused by fly ash.

Thermal responses of a concrete slab under hydrogen fuel cell vehicle fires in a semi-open car park

This work aims to investigate the thermal behaviors of the concrete ceiling slab of a semi-open car park exposed to localized fire in hydrogen fuel cell vehicles. For this purpose, a numerical simulation of the hydrogen fuel cell vehicle fire was performed in the Fluid Dynamic Simulator and then coupled with a subsequent thermal analysis of concrete structure carried out in ANSYS Mechanical APDL. In particular, an automatic procedure was used to extract the output of the fire simulation and apply them as boundary conditions of the thermal model. The one-way coupling procedure involving fire simulation and transient thermal analysis has been validated by comparing it with concrete temperatures of a previous test study. Then, two parameters, the diameter of thermal pressure relief devices (1 mm, 2 mm, 3 mm, and 4 mm) and fire spread time between vehicles (0 min, 20 min, and 30 min), are taken into account to study the thermal properties of concrete. The analysis revealed that an increase in the nozzle diameter of the thermal pressure relief device leads to a rise in the maximum concrete surface temperature. The simulation results also showed that the maximum value of the heat release rate increases with a higher value of the nozzle diameter of the thermal pressure relief device and a shorter fire spread time between vehicles.

Wave–structure interaction by a two–way coupling between a fully nonlinear potential flow model and a Navier–Stokes solver

A two-way domain decomposition coupling procedure between a fully nonlinear potential flow model and a Navier–Stokes solver capturing the free surface with a Volume of Fluid method is used to study wave–structure interaction applied to offshore wind turbines. Away from the structure, the large-scale inviscid wave field is modeled by the potential code. Wave generation and absorption in this 3D hybrid model take place in the outer potential domain. The codes exchange data in the region around their common boundaries. Through the two-way coupling, waves propagate in and out of the viscous subdomain, making the hybrid algorithm suitable to study wave diffraction on marine structures, while keeping the viscous subdomain small. Each code uses its own mesh and time step. Subdomains are overlapping, therefore continuity conditions on velocity and free surface have to be verified on two distinct coupling surfaces at any time. Parallel implementation with communications between the models relying on the Message Passing Interface library allows calculations on large spatial and temporal scales. The coupling algorithm is first tested for regular nonlinear waves and then applied to simulate wave loads exerted on a vertical monopile in 3D. Attention is paid to the high-order components of the horizontal force.

GeoTaichi: A Taichi-powered high-performance numerical simulator for multiscale geophysical problems

This study introduces GeoTaichi, an open-source high-performance numerical simulator designed for addressing multiscale geophysical problems. By leveraging the power of the Taichi parallel language, GeoTaichi maximizes the utilization of modern computer resources on multicore CPU and GPU architectures. It offers robust and reliable modules for the discrete element method (DEM), material point method (MPM), and coupled material point-discrete element method (MPDEM). These modules enable efficient solving of large-scale problems while being implemented in pure Python. The design philosophy of GeoTaichi focuses on creating a framework that is readable, extensible, and user-friendly. This paper highlights the coupling procedure of MPDEM, the code structures, and the most important features of GeoTaichi. Rigorous benchmark tests have been conducted to verify the validity and robustness of GeoTaichi. Additionally, the performance of GeoTaichi is compared with similar software tools in the field, underscoring a notable improvement in both computational efficiency and memory savings when compared to existing alternatives. Program summaryProgram title: GeoTaichiCPC Library link to program files:https://doi.org/10.17632/858bmcf7j6.1Developer's repository link:https://github.com/Yihao-Shi/GeoTaichiLicensing provisions: GNU General Public License v3.0Programming language: PythonNature of problem: The simulations of large-deformation geophysical flows and their interaction with structures play a crucial role in the field of geophysics. To address the complexities of these nonlinear problems, the discrete element method (DEM), material point method (MPM), and their coupling (MPDEM) have proven to be highly suitable numerical schemes. However, these schemes impose substantial computational demands, necessitating the development of an efficient framework that can harness modern computer resources on multicore CPU and GPU architectures.Solution method: The open-source code GeoTaichi implements the DEM, MPM, and coupled MPDEM, encompassing a range of constitutive models and contact laws for different geologic materials. The clump particle model is also introduced in DEM to solve granular mechanics involving complex-shaped particles. One significant advantage of GeoTaichi is its utilization of the Taichi parallel language, which is designed to be user-friendly and easily extensible for customized applications.

A computational- experimental model of reactor kinetic for investigating the linearity response of in-core neutron detectors of a low power research reactor

In this study, the linear response of fission chamber (FC) neutron detectors in Isfahan miniature neutron source reactor (MNSR) is investigated through experiments and calculations at different powers of the reactor. The linearity of the response of the main neutron detector in the MNSR is important due to its safety functions in reactor power control. Additionally, determining the linear response region of this detector presents a linear neutron dosimetry field even outside of the reactor core, i.e. at the outlet of external beam tubes. Moreover, it is very difficult to remove and calibrate this neutron detector that has been installed in the reactor core for a long time. For this purpose, an alternative method for measuring the linearity of the response of a neutron detector is extended by investigating the kinetic behavior of reactor. The aim of this method is to calculate the delayed neutrons population in the reactor core and compare with the FC detector response. In this method, the numerical solution method is used to solve the point kinetic equation with 15 delayed neutron groups (6 delayed neutron groups and 9 photo-neutron groups) after inserting a large negative reactivity into the MNSR core by considering temperature and xenon reactivity feedbacks during a coupling procedure. To obtain the xenon reactivity feedback, xenon concentration is calculated by coupling the 135Xe and 135I production equations and the εpPFnlPTnl parameter is obtained by an experimental method. Furthermore, the value of fission cross section (Σf) is calculated using a validated model in the Dragon code. The large reactivities are inserted at two initial power of 150 W and 30 kW to investigate the response of the main FC neutron detector in a cold xenon-free condition and by considering temperature and xenon reactivity feedbacks, respectively. The results demonstrate that the response of the MNSR FC detector is linear in the neutron flux range between 5 × 107 to 1 × 1012 n.cm−2.s−1, which is equivalent to reactor power of 1.5 W to 30 kW. This innovative method can be applied to calibrate the neutron detectors in other research and power reactors.

Pentetic acid derived dual purpose fluorescent carbon dots for pH responsive drug delivery and antioxidant proficiency

Heteroatom-doped surface-engineered carbon dots provide substantial potential, not only in their fluorescence sensing capabilities but also as nanocarriers for medicinal compounds and in exhibiting antioxidant behaviour. Here we describe a way to make naturally occurring carbon dots (PACDs) utilizing pentetic acid and gelatin in a one-step thermal coupling procedure. Antioxidant activity, biocompatibility, and colloidal stability were all highlighted by the PACDs. In order to assess the PACDs' drug transport capabilities, anticancer model drug molecules were also attached to their surface. Prolonged release patterns were seen in the drug-containing PACDs, indicating that they could be used for controlled drug delivery. Cumulative release data has been fitted into the Higuchi and Weibull models to understand the medication delivery process. The PACDs showed release characteristics that were sensitive to changes in pH; at acidic pH, the release profile could be more precisely controlled (∼28 %) than at alkaline pH (∼59 %). At PACDs concentrations <1 mg/mL, the radical activity is >80 % active; however this activity is greatly affected by the concentration. Because of their low toxicity to living human cell lines, PACDs are an attractive and versatile nano-vector for use in biomedical studies.

Quality assurance for focused ultrasound-induced blood-brain barrier opening procedure using passive acoustic detection

Focused ultrasound (FUS) combined with microbubbles is a promising technique for noninvasive, reversible, and spatially targeted blood-brain barrier opening, with clinical trials currently ongoing. Despite the fast development of this technology, there is a lack of established quality assurance (QA) strategies to ensure procedure consistency and safety. To address this challenge, this study presents the development and clinical evaluation of a passive acoustic detection-based QA protocol for FUS-induced blood-brain barrier opening (FUS-BBBO) procedure. Ten glioma patients were recruited to a clinical trial for evaluating a neuronavigation-guided FUS device. An acoustic sensor was incorporated at the center of the FUS device to passively capture acoustic signals for accomplishing three QA functions: FUS device QA to ensure the device functions consistently, acoustic coupling QA to detect air bubbles trapped in the acoustic coupling gel and water bladder of the transducer, and FUS procedure QA to evaluate the consistency of the treatment procedure. The FUS device passed the device QA in 9/10 patient studies. 4/9 cases failed acoustic coupling QA on the first try. The acoustic coupling procedure was repeatedly performed until it passed QA in 3/4 cases. One case failed acoustic coupling QA due to time constraints. Realtime passive cavitation monitoring was performed for FUS procedure QA, which captured variations in FUS-induced microbubble cavitation dynamics among patients. This study demonstrated that the proposed passive acoustic detection could be integrated with a clinical FUS system for the QA of the FUS-BBBO procedure. National Institutes of Health R01CA276174, R01MH116981, UG3MH126861, R01EB027223, R01EB030102, and R01NS128461.

An investigation of the effect of high temperature on the strength compression and ultrasonic pulse velocity of self-compacting concrete

One of the most significant mechanisms of deterioration in self-compacting concrete (SCC) structures over the course of their service life is exposure to elevated temperatures. For this reason, the effects of elevated temperatures on the residual mechanical properties of SCC made of various cementitious additions (silica fume (SF), limestone filler (LF), and crushed dune sand (SD)) was investigated via partially substituting amount of Portland cement in the SCC. The SCC was formed and heated with the coupling procedure of heating-cooling at ambient temperatures ranging from 20, 150, 400, 600, and 800 °C. The compressive strength (CS) and ultrasonic pulse velocity (UPV) were measured after cooling at room temperature of 20 °C. The findings show that CS and UPV exhibit intriguing outcomes for all self-compacting concretes. Otherwise, the UPV decreases with temperature in the range of 250 and 800 °C. In addition, at 600 °C, SCC-SF and SCC-SD have the highest residual compressive strengths, 31.20 and 23.80 MPa, respectively.

Cp*Ir(III) complexes catalyzed solvent-free synthesis of quinolines, pyrroles and pyridines via an ADC strategy.

A trio of Ir(III) complexes that are held together by a picolinamidato moiety were created. In our earlier research, we demonstrated the catalytic activity of the complexes for producing alpha-alkylated ketones from a ketone or secondary alcohol with a primary alcohol in the presence of a catalytic amount of a Cp*Ir(III) catalyst and tBuOK in toluene at 110 °C using the hydrogen-borrowing technique. Earlier many research groups had synthesized quinoline, pyrrole, and pyridine derivatives using 2-amino alcohol and ketone or secondary alcohol derivatives as starting materials, but in all those cases the reaction conditions are not suitable in terms of green synthesis like more catalyst loading, base loading, long reaction time, and high temperature. In addition, most of the reactions contain phosphine a hazardous by-product, along with the catalyst. Keeping in mind these shortcomings, we tried to expand the use of our catalysts after achieving an excellent result in our previous work, and we were successful in producing quinoline, pyrrole, and pyridine derivatives through acceptor-less dehydrogenative coupling (ADC) procedures at 90-110 °C under neat/solvent-free conditions and achieved good to exceptional yields of those nitrogen-containing heterocycles. This methodology is attractive because it is environmentally benign and allows for the "green" synthesis of nitrogen-containing heterocycles. All that is required is a modest quantity of catalyst and base, and the by-products are merely H2O and H2.

Synthesis of novel phthalazine-based derivatives with potent cytotoxicity against HCT-116 cells through apoptosis and VEGFR2 inhibition.

The parent ethyl 3-(4-benzyl-1-oxophthalazin-2(1H)-yl) propanoate (3) has 25 compounds. Their respective mono, dipeptides and hydrazones derivatives were produced by chemoselective N-alkylation via addition reaction of 4-benzylphthalazin-1(2H)-one (2) with ethyl acrylate and anhydrous potassium carbonate to give ethyl 3-(4-benzyl-1-oxophthalazin-2(1H)-yl) propanoate (3). The ester 3 was hydrazinolyzed to give the corresponding hydrazide 3-(4-benzyl-1-oxophthalazin-2(1H)-yl) propanehydrazide (5), then azide 6 coupled with amino acid ester hydrochloride and/or amines to afford several parent esters 8a-c, then a series of hydrazinolyzed reactions occurred to give corresponding hydrazides 9a-c. The hydrazide 9a was subjected to the azide coupling procedure, which resulted in the formation of various dipeptides. Subsequently, it was condensed with various aldehydes to yield hydrazone derivatives 13a-d. Interestingly, compounds 9c, 12b, and 13c exhibited potent cytotoxicity with IC50 values of 1.58, 0.32 and 0.64 μM compared to sorafenib (IC50 = 2.93 μM). Compound 12b exhibited potent VEGFR2 inhibition by 95.2% with an IC50 value of 17.8 μM compared to sorafenib (94.7% and IC50 of 32.1 μM). For apoptosis activity, 12b-treatment induced apoptosis in HCT-116 cells by 21.7-fold, arresting the cell proliferation at S-phase. Finally, it formed a good binding affinity towards VEGFR2 protein with a binding energy of -10.66 kcal mol-1, and it formed binding interactions with the key interactive amino acids.

Surface Plasmon Resonance Binding Study on the Interaction of Acetazolamide and Bovine Serum Albumin

Objective: Serum albumins are major plasma proteins in systemic blood circulation and act as transport proteins for endogenous and exogenous compounds such as drugs. In pharmaceutical applications, it is essential to characterize how drugs bind to serum albumin in the evaluation of drug candidates. Surface plasmon resonance (SPR) is fast, real-time, label-free optical based detection technique that offers the monitoring of molecular interactions, analyzing binding reactions and determining the affinity constants with real-time and high sensitivity. Acetazolamide (AZA) is used in the treatment of epilepsy and glaucoma.&#x0D; Methods: To determine the binding kinetics of AZA-Bovine serum albumin (BSA) interaction, (i) SPR gold sensor surface was functionalized, (ii) amine coupling procedure was applied to activate the surface group and BSA was immobilized on functionalized sensor surface, (iii) the concentration series of AZA (10, 25, 50, 75, 100, 150, 200 and 250 µM) was injected to SPR system and (iv) kinetic values were measured using the software of SPR system. &#x0D; Results: 5 mM MUA was coated for surface functionalization. 250 µg/mL BSA as ligand, 30 µL/min flow rate, 1X PBS buffer (pH 7.4) and 10 mM acetate buffer (pH 5.2) as running and coupling buffers, respectively, were performed for SPR binding study. According to result, equilibrium constant (KD) of AZA-BSA was determined as 67.72 µM.&#x0D; Conclusion: In this study, we investigated the AZA-BSA binding interaction using SPR system based on Kretchmann configuration. The study designed with fast, label-free and real-time approach will provide valuable knowledge for pharmaceutical and clinical applications.

Fractional cosmic strings

Topological defects are investigated in the framework of quantum gravity models based on the hypothesis of an effective fractal dimension of the Universe. From a minimal coupling procedure, the tools of fractional calculus are used to determine the geometry associated to a fractional cosmic string. Several results for the propagation of light are discussed, notably the light-deviation angle due to the defect and the geodesics of light.

The use of microwave radiations and propylphosphonic anhydride (T3P®) for rapid and highly yielding amide bond formation and peptide coupling

An improved, fast, and efficient procedure for amide bond formation and peptide coupling is reported leading to the expected corresponding derivatives in good to excellent isolated yields ranging from 26 to 90%. The outcome of the reaction was also investigated in relation to the influence of different parameters such as the nature of the solvent, the temperature as well as the amine/carboxylic acid couple involved or the hydrolysis conditions.

Bimetallic Cu/Pd(ppm)-catalyzed Suzuki-Miyaura couplings: DFT studies on mechanism, roles of Pd(ppm) and ligands

Transition metal-catalyzed Suzuki-Miyaura coupling (SMC) reaction is an important method to constructe the C-C bond. In this work, the mechanisms of SMC between ArI and ArB(OH)2 (Ar=C6H4(OCH3)) catalyzed by single [Cu] catalyst and bimetallic [Cu]/[Pd] catalysts have been studied by DFT calculations. Comparing to the N, O-bidentate ligand, the N, P-bidentate ligand coordinated [L12-Cu] catalyst is not efficient for the above reaction, due to the high energy barrier of the C-C coupling procedure. The different coordination mode of the N, O-bidentate ligand increases the positive charge of coupling C atom, lowering the energy barrier when catalyzed by [L13-Cu]. The [Cu]/[Pd] catalyzed process involves two cycles: LCuAr is obtained from the [Cu] catalyzed cycle by the reaction between ArB(OH)2 and [L12Cu]. The [Pd] catalyzed cycle consists of four steps: L12Pd(0) insertion into C-I bond by oxidation addition, coordination transformation, transmetallation between LCuAr and ArPdI, and C-C coupling by reductive elimination. In these two cycles, the coordination transformation of the Pd is the rate-determining step. The participation of [Pd] catalyst changes the C-C coupling process from the Cu center to the Pd center, which lowers the energy barrier and makes the reaction become easier.

Application of In Silico Trials for the Investigation of Drug Effects on Cardiomyopathy-Diseased Heart Cycle Properties

In this paper, we present the abilities of an in silico platform used to simulate the effects of different drugs on heartbeat cycle performance. The platform is based on a finite element modelling approach with the fluid–solid interaction implemented using a loose coupling procedure. Active mechanical stresses are calculated using the Hunter excitation model while the passive mechanical stresses are calculated using a recently introduced experiment-based material model for the heart tissue. The applicability of the platform is illustrated using a simple parametric model of the left ventricle. The simulations are performed using parameters that are specific to drugs such as digoxin, mavacamten, 2-deoxy adenosine triphosphate, and disopyramide, with the concentration of calcium in the cardiac cells affected by these drugs given as an input function. The results are obtained for two geometries mimicking patients with hypertrophic and dilated cardiomyopathy, and also for different inlet/outlet boundary conditions simulating different drug effects at the macroscopic level. Using in silico simulations with virtual patients, it is possible to evaluate the influence of different drugs on cardiac output and ejection fraction. This approach can significantly reduce computational costs with an acceptable solution accuracy compared to approaches coupling finite element and biophysical muscle model methods that are used to calculate drug effects at the micro level.